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Serum voriconazole

Anette Veringa, Sanne Geling, Lambert F R Span, Karin M Vermeulen, Jan G Zijlstra, Tjip S van der Werf, Jos G W Kosterink, Jan-Willem C Alffenaar
An important element in antimicrobial stewardship programmes is early switch from intravenous (i.v.) to oral antimicrobial treatment, especially for highly bioavailable drugs. The antifungal agent voriconazole is available both in i.v. and oral formulations and bioavailability is estimated to be >90% in healthy volunteers, making this drug a suitable candidate for such a transition. Recently, two studies have shown that the bioavailability of voriconazole is substantially lower in patients. However, for both studies various factors that could influence the voriconazole serum concentration, such as inflammation, concomitant intake of food with oral voriconazole, and gastrointestinal complications, were not included in the evaluation...
November 23, 2016: International Journal of Antimicrobial Agents
Brad Moriyama, Aniwaa Owusu Obeng, Julia Barbarino, Scott R Penzak, Stacey A Henning, Stuart A Scott, José A G Agúndez, John R Wingard, Howard L McLeod, Teri E Klein, Shane Cross, Kelly E Caudle, Thomas J Walsh
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas, poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx...
December 16, 2016: Clinical Pharmacology and Therapeutics
Matxalen Vidal-García, Pilar Sáncehez-Chueca, María Pilar Domingo, Carlos Ballester, Lourdes Roc, Isabel Ferrer, María José Revillo, Julián Pardo, Eva María Gálvez, Antonio Rezusta
BACKGROUND: Disseminated invasive aspergillosis is an exceptional finding in immunocompetent hosts. As in immunocompromised patients, it has high mortality rates. Early diagnostic methods are required in order to properly manage the patient. Bis(methylthio)gliotoxin (bmGT) is a novel biomarker, useful in onco-hematological patients. CASE REPORT: A 70-year-old male, with non-insulin dependent type II diabetes mellitus and a past surgery history of aortic valve replacement with coronary by-pass five years ago, was seen in the emergency department with blurred vision...
December 8, 2016: Revista Iberoamericana de Micología
Beibei Shao, Yongcheng Ma, Qiaoyan Li, Yimeng Wang, Zunmin Zhu, Hongwei Zhao, Jun Sun, Lingfang Dong, Yingli Zhu, Ningmin Zhao, Yuhua Qin
1. Polymorphisms of cytochrome P450 2C19 (CYP2C19) is an important factor contributing to variability of voriconazole pharmacokinetics. Polymorphisms of CYP3A4, CYP3A5, CYP2C9 and non-genetic factors such as age, gender, body mass index (BMI), transaminase levels, concomitant medications might also affect voriconazole initial steady serum trough concentration (VICmin) in haematological patients, but the effects were not clear. 2. Eighteen single-nucleotide polymorphisms in CYP2C19, CYP3A4, CYP3A5, CYP2C9 were genotyped...
January 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Sankha S Basu, Athena Petrides, Donald S Mason, Petr Jarolim
BACKGROUND: Triazole antifungals are essential to the treatment and prophylaxis of fungal infections. Significant pharmacokinetic variability combined with a clinical need for faster turnaround times has increased demand for in-house therapeutic drug monitoring of these drugs, which is best performed using mass spectrometry-based platforms. However, technical and logistical obstacles to implementing these platforms in hospital laboratories have limited their widespread utilization. Here, we present the development and validation of a fast and simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to measure fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole in human serum suitable for incorporation into a hospital clinical laboratory...
November 21, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Alessandro Busca, Livio Pagano
Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan...
2016: Mediterranean Journal of Hematology and Infectious Diseases
Anette Veringa, Mendy Ter Avest, Lambert F R Span, Edwin R van den Heuvel, Daan J Touw, Jan G Zijlstra, Jos G W Kosterink, Tjip S van der Werf, Jan-Willem C Alffenaar
BACKGROUND: During an infection or inflammation, several drug-metabolizing enzymes in the liver are down-regulated, including cytochrome P450 iso-enzymes. Since voriconazole is extensively metabolized by cytochrome P450 iso-enzymes, the metabolism of voriconazole can be influenced during inflammation via reduced clearance of the drug, resulting in higher voriconazole trough concentrations. OBJECTIVE: To investigate prospectively the influence of inflammation on voriconazole metabolism and voriconazole trough concentrations...
January 2017: Journal of Antimicrobial Chemotherapy
Miriam T Levine, Pranatharthi H Chandrasekar
Voriconazole use has increased since the drug's introduction in 2002, and new and unique adverse effects are emerging as patients undergo prolonged therapy. Most concerning is the increased risk of cutaneous malignancies, primarily squamous cell carcinoma (SCC); this risk is duration dependent and the associated malignancies tend to be more aggressive and multifocal. Voriconazole is also associated with phototoxicity (which may be a precursor to malignancy), periostitis, hallucinations and encephalopathy, peripheral neuropathy, alopecia, nail changes, hyponatremia, and other adverse effects...
November 2016: Clinical Transplantation
Tracy N Zembles, Nathan E Thompson, Peter L Havens, Bruce A Kaufman, Anna R Huppler
STUDY OBJECTIVE: To describe our experience with voriconazole in three patients younger than 2 years using an optimized dosing strategy for voriconazole that incorporates intensive therapeutic drug monitoring (TDM). DESIGN: Case series. SETTING: Large pediatric hospital. PATIENTS: Three patients younger than 2 years who received voriconazole therapy and had serum trough concentrations measured between January 1, 2010, and October 31, 2015...
October 2016: Pharmacotherapy
A Valentín, E Cantón, J Pemán, M E Fernandez-Rivero, M A Tormo-Mas, J P Martínez
OBJECTIVES: To evaluate the in vitro activity of anidulafungin combined with amphotericin B or voriconazole against Candida spp. biofilms. METHODS: Four Candida albicans, four Candida tropicalis, four Candida glabrata, two Candida parapsilosis and two Candida orthopsilosis blood isolates were tested by the microdilution chequerboard method combined with the XTT metabolic assay. Biofilm MIC was defined as the lowest concentration producing 50% metabolic inhibition with respect to control (BMIC50)...
December 2016: Journal of Antimicrobial Chemotherapy
Dustin T Wilson, V Paul Dimondi, Steven W Johnson, Travis M Jones, Richard H Drew
Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis...
2016: Therapeutics and Clinical Risk Management
Tomasz Urbanowicz, Bartłomiej Żabicki, Hanna Baszyńska-Wachowiak, Ewa Straburzyńska-Migaj, Robert Juszkat, Stefan Grajek, Marek Jemielity
Invasive aspergillosis is becoming increasingly prevalent, especially following transplantation. Invasive aspergillosis is associated with mortality. Successful therapy is related to early diagnosis and proper therapy. We present the case of a 61-year-old man suffering from invasive aspergillosis 2 months following heart transplantation. He was suffering from hypertrophic cardiomyopathy and he underwent orthotropic heart transplantation. He was readmitted to the Department of Cardiology 69 days following transplantation due to symptoms of productive cough for 5 days...
June 2016: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
Maria Siopi, Nikolaos Siafakas, Sophia Vourli, Johan W Mouton, Loukia Zerva, Joseph Meletiadis
BACKGROUND: Combination therapy of voriconazole with an echinocandin is often employed in order to increase the efficacy of voriconazole monotherapy. METHODS: Four clinical Aspergillus fumigatus isolates with different in vitro susceptibilities to voriconazole (MIC 0.125-2 mg/L) and anidulafungin (MEC 0.008-0.016 mg/L) were tested in an in vitro pharmacokinetic/pharmacodynamic model simulating human serum concentrations of standard dosages of voriconazole and anidulafungin...
November 2016: Journal of Antimicrobial Chemotherapy
Felipe Silva, Daniel Navea, Carolina Saias, Juan P Torres, Paula Catalán, Jorge Morales
BACKGROUND: Voriconazole (VCZ) serum drug levels (SDL) vary widely and are associated with increased mortality when they are below the therapeutic range for invasive aspergillosis (IA). AIM: To describe VCZ SDL in oncology pediatric patients in order to reach adequate concentrations for prophylaxis (≥ 0.5 mg/L) and treatment (≥ 1.0 y 2.0 mg/L) for IA and their relationship with toxicity. PATIENTS AND METHODS: Retrospective analysis of VCZ SDL and toxicities recorded in oncology pediatric patients between February 2013 and November 2014...
April 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Sevliya Öcal Demir, Serkan Atici, Gülşen Akkoç, Nurhayat Yakut, Nilay Baş İkizoğlu, Ela Erdem Eralp, Ahmet Soysal, Mustafa Bakir
Although voriconazole, a triazole antifungal, is a safe drug, treatment with this agent is associated with certain adverse events such as hepatic, neurologic, and visual disturbances. The current report presents two cases, one a 9-year-old boy and the other a 17-year-old girl, who experienced neurologic side effects associated with voriconazole therapy. Our aim is to remind readers of the side effects of voriconazole therapy in order to prevent unnecessary investigations especially for psychological and ophthalmologic problems...
2016: Case Reports in Infectious Diseases
(no author information available yet)
No abstract text is available yet for this article.
August 1, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Petra Füredi, Kristóf Kovács, Krisztina Ludányi, István Antal, Imre Klebovich
Human serum albumin (HSA) has attracted the most attention in the last decades as a new nanocarrier system of active pharmaceutical ingredients (API) due to its biocompatibility and high binding capacity to hydrophobic drugs. Voriconazole (VCZ), an antifungal agent with low water solubility, was selected to produce albumin based nanoparticles using nanoparticle albumin-bound technology (nab™-technology). Aim of our study was to study the development process of VCZ-loaded nanoparticles for parenteral drug delivery, such as homogenizing pressure, homogenizing cycle number and drug loading capacity...
August 20, 2016: International Journal of Pharmaceutics
Suvaporn Anugulruengkitt, Panruethai Trinavarat, Punchavit Chantranuwat, Suchada Sritippayawan, Chitsanu Pancharoen, Puthanakit Thanyawee
BACKGROUND: Invasive aspergillosis (IA) is a severe infection in immunocompromised patients. Recently, serum galactomannan has been widely used for diagnosis and voriconazole as an antifungal agent. The objective of this study is to describe clinical features and survival outcomes of IA. MATERIAL AND METHOD: A retrospective chart review of IA in patients younger than 18 years old at King Chulalongkorn Memorial Hospital, Thailand, was conducted. Clinical definitions were based on criteria oft he European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) 2008...
February 2016: Journal of the Medical Association of Thailand, Chotmaihet Thangphaet
Me-Linh Luong, Mona Al-Dabbagh, Andreas H Groll, Zdenek Racil, Yasuhito Nannya, Dimitra Mitsani, Shahid Husain
BACKGROUND: Voriconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of voriconazole TDM to guide therapy remains uncertain and controversial. We conducted a meta-analysis of studies assessing the relationship between voriconazole serum concentration and clinical outcomes of success and toxicity. METHODS: We searched bibliographic databases for studies on voriconazole serum concentrations and clinical outcomes...
July 2016: Journal of Antimicrobial Chemotherapy
Chi-Ching Tsang, Jasper F W Chan, Wai-Mei Pong, Jonathan H K Chen, Antonio H Y Ngan, Mei Cheung, Christopher K C Lai, Dominic N C Tsang, Susanna K P Lau, Patrick C Y Woo
"Engyodontium album" is an environmental saprobic mould and an emerging opportunistic pathogen able to cause both superficial and systemic infections. In this study, we isolated a mould from the skin lesion biopsy specimen of the right shin in a patient who received renal transplantation for end-stage renal failure with prednisolone, tacrolimus, and azathioprine immunosuppressant therapy. Histology of the skin biopsy showed mild squamous hyperplasia and neutrophilic infiltrate in the epidermis, active chronic inflammation in the dermis, and fat necrosis in the subcutis, with numerous fungal elements within the serum crusts...
October 1, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
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